Control of cell proliferation: evidence for negative control on estrogen-sensitive T47D human breast cancer cells

The human breast tumor cloned cell lines T47D-A8 and All are estrogen dependent for cell proliferation in the nude mouse model. In contrast, these cells multiplied at similar rates when grown in serum-free cultures, regardless of the presence of 17 beta-estradiol (3 X 10(-11) to 3 X 10(-8) M estradiol). Addition of 10% charcoal-dextran stripped human female serum to the culture medium resulted in a marked inhibition of cell proliferation. The addition of 3 X 10(-11) M estradiol overcame the inhibitory effect of serum. Similar results were obtained with the human breast tumor C7MCF7 cell line. Both cell lines contain similar estrophilin levels. The Kd of the estrophilin-estradiol complex was 0.39 X 10(-10) M for C7MCF7 cells and 4.4 X 10(-10) M for T47D-A11 cells. Maximal cell yields were achieved at 5 X 10(-12) M free estradiol levels in 10% charcoal-dextran stripped serum supplemented medium. These data are compatible with the following interpretation: (a) estradiol-sensitive cells are inhibited from proliferating by a serum-borne factor; and (b) estradiol neutralizes this inhibitory effect. This mechanism seems not to be mediated by estradiol binding to the cellular estrophilins because (a) the free estradiol levels needed for maximal response are significantly lower than the estrophilin Kds, and (b) maximal proliferation rates occur at similar estradiol concentrations for these three cell lines, regardless of the binding properties of their estrophilins.